Fish oils comprise a complex mixture of fatty acid moieties, mostly straight chain with an even number of carbon atoms. The fatty acids, usually present as their glycerides, are either saturated or mono- or polyunsaturated. Unlike vegetable oils and fats from terrestrial animals, which contain mainly fatty acids having a maximum of eighteen carbons and two or three double bonds, fish and marine mammal oils contain substantial amounts of fatty acids having twenty or twenty-two carbons and four, five or six double bonds. Among the fatty acid moieties unique to fish oils are the following omega-3 compounds: 18:4, 20:4, 20:5, 22:5, and 22:6, as well as other methylene-interrupted polyunsaturated fatty acids, such as 16:4nl and 16:3n4, which are present in significant amounts in fish oils. The omega-3 designation means that the first double bond begins at the third carbon counting from the methyl end of the chain; the designation n3 has the same meaning. In the number: number designation, the first number indicates chain length and the second number indicates how many double bonds are present. For example, 18:4 indicates a straight chain fatty acid having eighteen carbon atoms and four methylene-interrupted double bonds.
As indicated in U.S. Pat. No. 4,623,488, fish and marine oils are now recognized to be of potential nutritional and pharmacological value because they contain substantial quantities of polyunsaturated acids and as indicated in the paper by Nilsson et. al., "Fractionation of Menhaden Oil Ethyl Esters Using Supercritical Fluid CO.sub.2 ", Journal of the American Oil Chemists' Society, Vol. 65, No. 1, pages 109-117 (1988), clinical studies have noted a positive correlation between a diet high in fish oils containing polyunsaturated acids and a decreased risk of coronary and inflammatory diseases. Omega-3 all cis-5,8,11,14,17-eicosapentaenoic acid (EPA or 20:5n3) and all cis-4,7,10,13,16,19-docosahexaenoic acid (DHA or 22:6n3) in particular, and other polyunsaturated fatty acids having their double bonds in the methylene-interrupted cis-configuration, are thought to be the most beneficial.
Fish and fish oils are the major source of significant quantities of omega-3 eicosanoid precursors, such as EPA (shown below) and DHA. ##STR1## Fish oils should be contrasted with oils of vegetable origin which contain more saturated fatty acid and omega-6 fatty acid residues, sometimes implicated in the complex process that leads to cardiovascular disease.
Fish oils contain some eight or more omega-3 fatty acid residues and contain approximately 3-18% EPA and 3-25% DHA. The largest values for EPA and DHA are difficult to obtain consistently because the exact composition of a particular fish oil is quite variable depending on geographical location, season, sex, sexual maturity, and other factors. Even obtaining the same composition from the same species of fish is difficult. It is, therefore, highly desirable to provide omega-3 and other methyleneinterrupted polyunsaturated fatty acid containing substances having a high and reproducible content of specific individual methylene-interrupted fatty acid residues or combinations of methyleneinterrupted fatty acid residues, alone or with specific monoenoic or short/or medium-chain length fatty acids relatively free of saturated, monounsaturated and n6 polyunsaturated acid residues, which at best add unnecessary calories and at worst may cause deleterious effects.
Since polyunsaturated free fatty acids autoxidize rapidly, individual polyunsaturated fatty acids, such as omega-3 fatty acids, or mixtures thereof are available and are utilized as their methyl or ethyl esters. However, the suitability of the ester form as a dietary supplement has been questioned. An obvious alternative to using such lower alkyl esters is a triglyceride containing only the desired methylene-interrupted fatty acids, such as tri-EPA (trieicosapentaenoylglylcerol) or tri-DHA (tridocosahexaenoylglycerol) or a triglyceride having a high content of such omega-3 fatty acids.
Saturated fatty acids and their esters react readily to form triglycerides. Long-chain polyunsaturated acids and esters behave differently and are remarkably resistant to interesterification, especially in the final step of going from the diglyceride to the fully esterified triglyceride. It appears that the conformation of hydrocarbyl chains containing four, five, or six methylene-interrupted double bonds sterically hinders approach of the carboxyl group to the third hydroxyl group, and methods suitable for the synthesis of triglycerides from saturated fatty acids are in general unsuitable for the synthesis of glycerides from such polyunsaturated fatty acids.
It is known from the prior art that omega-3 triglycerides can be prepared by reacting glycerol with free fatty acids a elevated temperatures. However, polyunsaturated fatty acids are very susceptible to attack by oxygen at such elevated temperatures, and oxidation destroys the very structure that is believed responsible for the beneficial properties of omega-3 fatty acids while producing by-products which may be toxic.